crossing96/oncoscreening huggingface dataset:
Enhanced efficacy of bleomycin in bladder cancer cells by photochemical internalization.	Bleomycin is a cytotoxic chemotherapeutic agent widely used in cancer treatment. However, its efficacy in different cancers is low, possibly due to limited cellular internalization. In this study, a novel approach known as photochemical internalization (PCI) was explored to enhance bleomycin delivery in bladder cancer cells (human T24 and rat AY-27), as bladder cancer is a potential indication for use of PCI with bleomycin. The PCI technique was mediated by the amphiphilic photosensitizer disulfonated tetraphenyl chlorin (TPCS(2a)) and blue light (435 nm). Two additional strategies were explored to further enhance the cytotoxicity of bleomycin; a novel peptide drug ATX-101 which is known to impair DNA damage responses, and the protease inhibitor E-64 which may reduce bleomycin degradation by inhibition of bleomycin hydrolase. Our results demonstrate that the PCI technique enhances the bleomycin effect under appropriate conditions, and importantly we show that PCI-bleomycin treatment leads to increased levels of DNA damage supporting that the observed effect is due to increased bleomycin uptake. Impairing the DNA damage responses by ATX-101 further enhances the efficacy of the PCI-bleomycin treatment, while inhibiting the bleomycin hydrolase does not.	bladder
APPEX: analysis platform for the identification of prognostic gene expression signatures in cancer.	SUMMARY: Because cancer has heterogeneous clinical behaviors due to the progressive accumulation of multiple genetic and epigenetic alterations, the identification of robust molecular signatures for predicting cancer outcome is profoundly important. Here, we introduce the APPEX Web-based analysis platform as a versatile tool for identifying prognostic molecular signatures that predict cancer diversity. We incorporated most of statistical methods for survival analysis and implemented seven survival analysis workflows, including CoxSingle, CoxMulti, IntransSingle, IntransMulti, SuperPC, TimeRoc and multivariate. A total of 236 publicly available datasets were collected, processed and stored to support easy independent validation of prognostic signatures. Two case studies including disease recurrence and bladder cancer progression were described using different combinations of the seven workflows. AVAILABILITY AND IMPLEMENTATION: APPEX is freely available at http://www.appex.kr. CONTACT: kimsy@kribb.re.kr SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.	bladder
NBS1 Glu185Gln polymorphism and susceptibility to urinary system cancer: a meta-analysis.	A number of studies have investigated the association between the NBS1 Glu185Gln (rs1805794, 8360 G>C) polymorphism and risk for urinary system cancer including bladder cancer, prostate cancer, and renal cell cancer; however, the findings are conflicting. We conducted a meta-analysis focusing on eight published studies with 3,542 cases and 4,210 controls to derive a more precise evaluation of the relationship between the NBS1 Glu185Gln polymorphism and urinary system cancer susceptibility. Overall, the NBS1 Glu185Gln polymorphism was significantly related to increased risk for urinary system cancer (homozygous model: odds ratio (OR)=1.23, 95 % confidence interval (95% CI)= 1.05–1.44, p=0.011; heterozygous model: OR=1.14, 95% CI=1.04–1.26, p=0.008; dominant model: OR=1.16, 95% CI=1.05–1.27, p=0.002; and Gln vs. Glu: OR=1.12, 9% CI=1.04–1.20, p=0.002) and further stratification analysis indicated an increased risk for bladder cancer (heterozygous model: OR=1.13, 95% CI=1.02–1.26, p=0.022; dominant model: OR=1.14, 95% CI=1.03–1.26, p=0.014; and Gln vs. Glu: OR=1.09, 95%CI=1.01–1.18, p=0.023) and Caucasian populations (homozygous model: OR=1.33, 95% CI=1.11–1.59, p=0.002; heterozygous model: OR=1.16, 95% CI=1.04–1.30, p=0.009; dominant model: OR=1.19, 95% CI=1.07–1.32, p=0.001; and Gln vs. Glu: OR=1.15, 95% CI=1.06–1.25, p<0.001). Despite some limitations, this meta-analysis established some solid statistical evidence for the association between NBS1 Glu185Gln polymorphism and increased risk for urinary system cancer, especially for bladder cancer, but more well-designed prospective studies are needed to further verify our findings.	bladder
The prognostic value and therapeutic target role of stathmin-1 in urinary bladder cancer.	BACKGROUND: The oncoprotein-18/stathmin 1 (STMN1), involved in cell progression and migration, is associated with clinical outcome in breast cancer. Here we aim to investigate its clinical significance in urinary bladder cancer and its possibilities as a therapeutic target. METHODS: Immunohistochemical analyses of STMN1 protein expression were performed in three patient cohorts: cohort I (n=115 Ta, n=115 T1, n=112 T2-4 stages), cohort II, based on randomised controlled trials (n=239 T1-T4), and cohort III of primary tumour/matched metastasis (n=90 T1-T4). The effects of STMN1 on cell proliferation and migration were evaluated in the urinary bladder cancer cell line, T24, by inhibiting STMN1-cellular expression using siRNA. RESULTS: In cohort I, high STMN1 expression correlated to shorter disease-specific survival hazard ratio (HR)=2.04 (95% confidence interval (CI) 1.13-3.68; P=0.02), elevated p53- (P<0.001) and Ki67-protein levels (P<0.001). The survival result was validated in cohort II: HR=1.76 (95% CI 1.04-2.99; P=0.03). In the metastatic bladder cancer material, 70% of the patients were STMN1-positive in both the primary tumour and matched metastases. In vitro, the growth and migration of the T24 cells were significantly reduced (P<0.01, P<0.0001, respectively), when transfecting the cells with STMN1-siRNA. CONCLUSIONS: STMN1 protein expression has prognostic significance but is primarily a potential treatment target in urinary bladder cancer.	bladder
Summary of the 8th Annual Bladder Cancer Think Tank: Collaborating to move research forward.	"OBJECTIVES: The 8th Annual Bladder Cancer Think Tank (BCAN-TT) brought together a multidisciplinary group of clinicians, researchers, and patient advocates in an effort to advance bladder cancer research. METHODS AND MATERIALS: With the theme of ""Collaborating to Move Research Forward,"" the meeting included three panel presentations and seven small working groups. RESULTS: The panel presentations and interactive discussions focused on three main areas: gender disparities, sexual dysfunction, and targeting novel pathways in bladder cancer. Small working groups also met to identify projects for the upcoming year, including: (1) improving enrollment and quality of clinical trials; (2) collecting data from multiple institutions for future research; (3) evaluating patterns of care for non-muscle-invasive bladder cancer; (4) improving delivery of care for muscle-invasive disease; (5) improving quality of life for survivors; (6) addressing upper tract disease; and (7) examining the impact of health policy changes on research and treatment of bladder cancer. CONCLUSIONS: The goal of the BCAN-TT is to advance the care of patients with bladder cancer and to promote collaborative research throughout the year. The meeting provided ample opportunities for collaboration among clinicians from multiple disciplines, patients and patient advocates, and industry representatives."	bladder
Toward online adaptive hyperthermia treatment planning: correlation between measured and simulated specific absorption rate changes caused by phase steering in patients.	PURPOSE: Hyperthermia is the clinical application of heat, in which tumor temperatures are raised to 40°C to 45°C. This proven radiation and chemosensitizer significantly improves clinical outcome for several tumor sites. Earlier studies of the use of pre-treatment planning for hyperthermia showed good qualitative but disappointing quantitative reliability. The purpose of this study was to investigate whether hyperthermia treatment planning (HTP) can be used more reliably for online adaptive treatment planning during locoregional hyperthermia treatments. METHODS AND MATERIALS: This study included 78 treatment sessions for 15 patients with non-muscle-invasive bladder cancer. At the start of treatments, temperature rise measurements were performed with 3 different antenna settings optimized for each patient, from which the absorbed power (specific absorption rate [SAR]) was derived. HTP was performed based on a computed tomography (CT) scan in treatment position with the bladder catheter in situ. The SAR along the thermocouple tracks was extracted from the simulated SAR distributions. Correlations between measured and simulated (average) SAR values were determined. To evaluate phase steering, correlations between the changes in simulated and measured SAR values averaged over the thermocouple probe were determined for all 3 combinations of antenna settings. RESULTS: For 42% of the individual treatment sessions, the correlation coefficient between measured and simulated SAR profiles was higher than 0.5, whereas 58% showed a weak correlation (R of <0.5). The overall correlation coefficient between measured and simulated average SAR was weak (R=0.31; P<.001). The measured and simulated changes in average SAR after adapting antenna settings correlated much better (R=0.70; P<.001). The ratio between the measured and simulated quotients of maximum and average SARs was 1.03 ± 0.26 (mean ± SD), indicating that HTP can also correctly predict the relative amplitude of SAR peaks. CONCLUSIONS: HTP can correctly predict SAR changes after adapting antenna settings during hyperthermia treatments. This allows online adaptive treatment planning, assisting the operator in determining antenna settings resulting in increased tumor temperatures.	bladder
Lymph node metastases in patients with urothelial carcinoma variants: influence of the specific variant on nodal histology.	OBJECTIVES: The effect that the presence of urothelial variant (UV) histologies has on the behavior of urothelial carcinoma remains poorly defined. The goal of this study is to examine the relationship between different histologic variants and the presence and histology of lymph node metastases. MATERIALS AND METHODS: Our institutional bladder cancer database was examined for all patients demonstrating UV at cystectomy performed between 2001 and 2012. Patients with primary bladder sarcoma, primary bladder adenocarcinoma, and squamous cell carcinoma were excluded. The cystectomy and nodal pathology reports were reviewed in node-positive cases with the goal of determining the relative percentages of UVs in the bladder and lymph nodes. RESULTS: Overall, 292 patients demonstrated UV at cystectomy. After excluding patients with primary adenocarcinoma, sarcoma, and squamous variants, 141 patients remained, of which 65 demonstrated node-positive disease. Of these node-positive patients, 57 had slides available for review. Node positivity was most common in the micropapillary (MP), clear cell urothelial carcinoma (CC), and plasmacytoid (PC) variants. Remaining variants demonstrated node-positive rates ranging from 11.1% to 37.5%. When nodes were positive, the variants found in the nodal metastases most commonly were MP, CC, glandular, nested, and lymphoepitheliomalike. Median lymph node density was highest in PC (33%) and CC (35%) variants, although these differences were not statistically significant. Variant histology predominated the nodal metastases regardless of predominance in bladder for the MP (84%) and CC (100%) variants. The PC variant exhibited the high incidence of positive surgical margins. CONCLUSION: Lymph node metastases were most common in the MP, CC, and PC variants. Variant histology was present and predominated nodal histology in most MP and CC cases. These results suggest that the variant histology itself may be driving lymphatic spread in MP and CC cases. Conversely, the PC variant may be a marker for locally advanced and aggressive disease rather than specifically influencing lymphatic spread.	bladder
Growth inhibition after exposure to transforming growth factor-β1 in human bladder cancer cell lines.	PURPOSE: Transforming growth factor-β1 (TGF-β1) plays a dual role in apoptosis and in proapoptotic responses in the support of survival in a variety of cells. The aim of this study was to determine the function of TGF-β1 in bladder cancer cells. MATERIALS AND METHODS: The role of TGF-β1 in bladder cancer cells was examined by observing cell viability by using the tetrazolium dye (MTT) assay after treating the bladder cancer cell lines 253J, 5637, T24, J82, HT1197, and HT1376 with TGF-β1. Among these cell lines, the 253J and T24 cell lines were coincubated with TGF-β1 and the pan anti-TGF-β antibody. Fluorescence-activated cell sorter (FACS) analysis was performed to determine the mechanism involved after TGF-β1 treatment in 253J cells. RESULTS: All six cell lines showed inhibited cellular growth after TGF-β1 treatment. Although the T24 and J82 cell lines also showed inhibited cellular growth, the growth inhibition was less than that observed in the other 4 cell lines. The addition of pan anti-TGF-β antibodies to the culture media restored the growth properties that had been inhibited by TGF-β1. FACS analysis was performed in the 253J cells and the 253J cells with TGF-β1. There were no significant differences in the cell cycle between the two treatments. However, there were more apoptotic cells in the TGF-β1-treated 253J cells. CONCLUSIONS: TGF-β1 did not stimulate cellular proliferation but was a growth inhibitory factor in bladder cancer cells. However, the pattern of its effects depended on the cell line. TGF-β1 achieved growth inhibition by enhancing the level of apoptosis.	bladder
Randomized trial of narrow-band versus white-light cystoscopy for restaging (second-look) transurethral resection of bladder tumors.	Narrow-band imaging (NBI) cystoscopy detects more bladder tumors than standard white-light imaging (WLI) cystoscopy, but it is unclear whether NBI improves transurethral resection (TUR) of bladder tumors. This study compares 2-yr recurrence-free survival (RFS) of patients with non-muscle-invasive bladder tumors following restaging TUR using NBI or WLI cystoscopy. Patients were randomized 1:1 to undergo NBI-assisted TUR (NBI-TUR) or WLI-assisted TUR (WLI-TUR). The main outcome was number of patients free of tumor recurrence after 2-yr follow-up and 2-yr RFS times. Of 254 patients, 127 underwent NBI-TUR and 127 had WLI-TUR. Within 2 yr, 22% of the patients in the NBI-TUR group recurred compared with 33% after WLI-TUR (p=0.05). The mean RFS time was 22 mo (95% confidence interval [CI], 20-23) for the NBI-TUR group versus 19 mo (95% CI, 18-21) for the WLI-TUR group (p=0.02). Limitations are that this was a single-surgeon study and that a 20% difference in the number of patients free of recurrence was not achieved, suggesting the study was underpowered. In addition, observer bias may have contributed to results because NBI-TUR was performed after both WLI and NBI cystoscopy was used to inspect the bladder. Although the results suggest reduced recurrence rates and improved RFS times after restaging NBI-TUR compared with WLI-TUR, a larger study is needed. PATIENT SUMMARY: Narrow-band imaging enhances visibility of bladder tumors over conventional white-light cystoscopy. This report compares transurethral resection of bladder tumors using narrow-band cystoscopy with white-light cystoscopy. The results show that narrow-band cystoscopy improves surgical removal of bladder tumors, which reduces the frequency of early and later tumor recurrences.	bladder
Predictive markers in bladder cancer: do we have molecular markers ready for clinical use?	Bladder cancer (BC) is a heterogeneous disease. Approximately 75% of patients present with non-muscle-invasive BC (NMIBC), which has a high recurrence rate and a low but unpredictable progression rate. Conversely, patients with muscle-invasive BC (MIBC) are at high risk for progression and cancer-specific mortality, but, again, disease behavior is unpredictable. To date, risk assessment for tumor recurrence and progression is based on clinico-pathological factors only. A risk assessment calculator that is based on several such parameters is available for NMIBC, but it has been reported to have potential flaws. In the last two decades, great effort has been made to evaluate the prognostic and predictive role of several molecular markers in MIBC and, even more so, in NMIBC, where the need for more precise risk stratification is urgently needed. This review addresses current evidence for the role of several molecular markers easily assessable by immunohistochemical techniques in prognosticating/predicting the outcome of NMIBC and MIBC. To date, because of divergent results among the many studies, no molecular marker has yet entered routine clinical practice; however, some of them (e.g., p53, pRb, p21, and survivin) have proved their predictive value in studies that included a homogeneous patient population on standardized treatment, and, therefore, are probably ready for clinical validation on a larger scale. Even more interesting is the possibility of constructing multimarker panels that could be used in routine clinical practice, as all these markers can easily be evaluated by immunohistochemistry on routine surgical pathology specimens. The molecular markers described herein hold promise for becoming widely available and cost-effective tools for reliable risk assessment, which would represent a great advancement in counseling patients, in selecting them for neoadjuvant and adjuvant treatments, and in determining their eligibility for clinical trials.	bladder
Critical analysis of the 2010 TNM classification in patients with lymph node-positive bladder cancer: influence of lymph node disease burden.	OBJECTIVES: In 2010, a new TNM staging system was published by American Joint Committee on Cancer, changing the nodal classification to include the presence of common iliac lymph node (LN) involvement as N3 category. The objective of this study was to define the capability of the current TNM nodal classification to separate patients with different prognostic stages and to evaluate the effect of LN disease burden. METHODS AND MATERIALS: A total of 93 patients with metastatic LNs after radical cystectomy and extended LN dissection for urothelial carcinoma of the bladder between 1999 and 2012 were included. The median follow-up was 21.5 months. The correlation between N3 and indicators of LN disease burden was analyzed using the Spearman correlation coefficient. Recurrence-free survival (RFS) and overall survival (OS) analysis was performed using the Kaplan-Meier and Cox proportional hazards methods. RESULTS: The presence of N3 disease was associated with higher number of metastatic LNs (7 vs. 2, P<0.01); however, this was highly variable and correlation coefficients between common iliac metastatic LNs and other lymphatic disease burden indicators demonstrated weak association (0.39-0.63). Patients with N1 lesions were found to have a distinct RFS and OS (P<0.01 and P = 0.01, respectively). A trend toward worse RFS (P = 0.07) and OS (P = 0.08) was observed in patients with N3 lesions. However, no difference in RFS or OS was found between patients with N2 and N3 lesions (P = 0.83 and 0.50, respectively). CONCLUSIONS: The N3 category in the current TNM classification defines a group of patients with high but heterogeneous disease burden. This may be the explanation for its lack of prognostic stratification when compared with N2 category bladder cancer.	bladder
Loss of PPM1A expression enhances invasion and the epithelial-to-mesenchymal transition in bladder cancer by activating the TGF-β/Smad signaling pathway.	The transforming growth factor-β (TGF-β) signaling pathway is believed to contribute to carcinoma development by increasing cell invasiveness and metastasis and inducing the epithelial-to-mesenchymal transition (EMT). Protein phosphatase PPM1A has been reported to dephosphorylate TGF-β-activated Smad2/3, thus inhibiting the TGF-β signaling pathway. In this study, we investigated the role of PPM1A in bladder cancer. PPM1A protein expression was analyzed in 145 bladder cancer specimens. The loss of PPM1A expression was predictive of poor survival and high muscle-invasiveness. PPM1A was more commonly deficient among muscle-invasive relapse samples compared to primary tumors in twenty paired bladder cancer tissues. Functional studies indicated that blockade of PPM1A through lentivirus-mediated RNA interference significantly promoted urinary bladder cancer (BCa) cell motility, the EMT in vitro and metastasis in vivo, and these effects were dependent on the TGF-β/Smad signaling pathway. The increase in p-Smad2/3 induced by TGF-β1 correlated with the degree of PPM1A depletion in BCa cells, which resulted in an altered expression profile of TGF-β-inducible genes. The correlations between PPM1A and biomarkers related to the TGF-β signaling pathway and tumor invasion were also detected in BCa samples. These results demonstrate that loss of PPM1A is associated with the development of tumor invasion in bladder cancer patients.	bladder
Glandular neoplasms of the urachus: a report of 55 cases emphasizing mucinous cystic tumors with proposed classification.	Published experience remains limited for glandular neoplasms of the urachus, especially mucinous cystic tumors. We reviewed 55 glandular urachal neoplasms to evaluate their clinical features and histopathologic spectrum and to devise a classification system for the mucinous cystic forms. Within the 55 cases studied, we observed 2 groups with differing clinical, gross, and histopathologic features. The first group, invasive, noncystic adenocarcinomas (n=24), had clinicopathologic features in accord with the known spectrum of urachal adenocarcinoma (mean age 50 y, female:male ratio 1.7, with recurrence or death from disease in 9/16 cases over a 45 mo mean follow-up). The second group, mucinous cystic tumors (n=31), morphologically resembled mucinous cystic tumors of the ovary and appeared classifiable by the same approach (mean age 47 y, female:male ratio 1.4) and included mucinous cystadenoma (n=4), mucinous cystic tumor of low malignant potential (n=22, including 2 cases with intraepithelial carcinoma), and mucinous cystadenocarcinoma with microscopic (n=4) or frank invasion (n=1). Follow-up information was available for 13 patients with mucinous cystic tumors (mean 41 mo); we observed no local recurrence or distant metastasis. This experience suggests that there is a distinct group of glandular, cystic tumors of the urachus that is classifiable in a manner similar to ovarian neoplasms and that has a favorable prognosis after complete excision. As with cystic neoplasms of other organs, rigorous sampling is recommended to identify potentially small foci of carcinoma that could be missed by inadequate sampling. Accordingly, classification based on methods other than complete surgical excision may be hazardous.	bladder